Reduction of carboxylic acids to alcohols is a fundamental transformation in organic chemistry. Traditionally, this reaction has been carried out using stoichiometric quantities of strong reducing agents such as lithium aluminum hydride or lithium triethylborohydride. The use of stoichiometric amounts of strong reductants is undesirable due to issues of reagent compatibility and the poor atom economy of the overall transformation.
An attractive alternative would be the direct hydrogenation of the carboxylic acid by dihydrogen. Unfortunately, carboxylic acids are among the most difficult carbonyl substrates to hydrogenate due to the low electrophilicity of the carbonyl carbon. It is unsurprising, therefore, that to date only two homogeneous systems for acid hydrogenation have been reported, both of which operate under relatively forcing conditions. Frediani and coworkers reported a series of ruthenium carbonyl-hydride clusters capable of hydrogenative coupling of various carboxylic acids to produce alkyl esters at 180° C. under 130 atm of H2. More recently, Leitner and coworkers reported a ruthenium tris-phosphine catalyst capable of hydrogenating bio-derived acids such as levulinic acid and itaconic acid. Depending on the reaction conditions (typically 100 atm H2, 160° C., Brønsted acid promoter) a variety of reduced products were formed, including lactones, alcohols, diols, and substituted tetrahydrofurans.
In view of the present state of the art, improved catalytic methods for direct hydrogentation by dihydrogen are desired.